Phase 2 in Pulmonary Arterial Hypertension Fails to Meet Endpoints

In January 2017, Eiger BioPharmaceuticals, Inc. initiated its Phase 2 Pulmonary Arterial Hypertension (PAH) treatment study, evaluating the effects of ubenimex.

Today, the company announced that results from the Phase 2 LIBERTY study demonstrated no improvement overall or in key subgroups for both the primary efficacy endpoint of pulmonary vascular resistance (PVR) and the secondary endpoint of 6-minute walk distance (6MWD). Throughout the preliminary analysis, no safety signals accredited to ubenimex were identified or acknowledged.

In the study, 45 patients were randomized in a 2:1 ratio to receive either 150 mg ubenimex or matching placebo, administered orally 3 times per day for 24 weeks. Patients who completed treatment through Week 24 were eligible to enroll in an open-label extension study to receive continued treatment.

PAH is characterized by increased pulmonary-artery pressure in the absence of the common causes of hypertension, like chronic heart, lung, or thromboembolic disease. Typically, symptoms include: dyspnea, fatigue, syncope, edemas in the legs, cyanosis, and heart palpatations.

Ubenimex is an oral, small-molecule inhibitor of leukotriene A4 hydrolase, which regulates the production of leukotriene B4 (LTB4). LTB4 is an inflammatory mediator implicated in PAH, and produced from leukocytes in response to inflammatory mediators. It is capable of inducing the adhesion and activation of leukocytes on the endothelium, allowing them to bind to and transfer it into the tissue.

Eiger has made clear its intentions to discontinue development of ubenimex in PAH based on these results, however, further analysis of data — including biomarkers – is ongoing.

"While we are disappointed with results from the LIBERTY study, we have always recognized that PAH is a complex disease and that this was a translational program," said David Cory, President and CEO in a press release.

"Eiger has a deep pipeline of products focused on rare diseases that was built to reduce risk against a single binary event. Phase 2 proof of concept has already been demonstrated in both Hepatitis Delta Virus (HDV) Infection and Post-Bariatric Hypoglycemia (PBH). We look forward to our upcoming End of Phase 2 meeting for HDV with the agency in February 2018. Topline results from the Phase 2, 28 day PREVENT study in PBH as well as for the Phase 2 ULTRA study in primary and secondary lymphedema will be reported in the second half of 2018. The company will direct all resources to advance these important efforts."

Per the American Lung Association, it is estimated that 50% of people with PAH die within 5 years of diagnosis, and average survival is 3 years. At present, there are several orphan drugs approved for the treatment of PAH, including: Uptravi (selexipag), Opsumit (macitentan), and Adempas (ricociguat).

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